Diseased and damaged parts of the body are best repaired or replaced with an organism's own tissue. Physicians and surgeons routinely replace tissue, organs or bone through delicate and complicated medical procedures. Appropriate donor tissues are generally procured elsewhere: either from the recipient's own body (autograft); from a second donor (allograft); or, in some cases, from a donor of another species (xenograft). Tissue transplantation is costly, and suffers from significant failure rates, an increasing risk of disease transmission and inadequate supplies of donor tissues. Therefore, in response to these current transplantation issues, use of artificial or synthetic medical implant devices, fabricated through tissue engineering technology, has been the subject of considerable attention.
Although implant devices can be used in some instances as an alternative to donor-based transplants, they too often produce unsatisfactory results because of the implant's incompatibility with the body and inability to function properly. For example, polymeric vascular graft inner-wall surfaces are not usually adhesive enough to completely prevent cellular or other bioactive coatings from unwanted migration along the blood vessel's inner-wall surface. Lack of cellular adhesion to the vascular graft's synthetic surface sets-up conditions that increase the risk of thrombosis, hyperplasia and other medical/surgical procedural complications. Vascular grafts require non-thrombogenic surfaces. Vascular implant materials must have a biocompatible surface, allowing only a minimal response of platelets to the vessel's inner surface; and, at the same time, have the correct fluid dynamics at the vessel wall-blood interface to eliminate or reduce unwanted turbulence and eddy formation. In other types of implants, unwanted fibrogenesis can occur, encasing the implant. The implant will then have an increased risk of rejection and other medical complications. Thus, efforts have been directed at application of biocompatible coatings, such as Teflon, onto implant surfaces.
Materials from which implant devices are made (e.g., metals and polymers) are often not manufactured with surface conditions conducive to optimal functionality (e.g., adhering biocompatible materials, cellular coatings or host tissue); they require some form of conditioning and/or pretreatment that will physically enhance the surface to promote its adhesive properties to the desired tissue or coating material.
Conventional methods for surface treatment include physical, chemical or electrochemical techniques. Surface modification with physical techniques can be achieved with abrasives, such as found in sand blasting which produces macroporous surfaces, or machining with equipment, such as milling machines that also produce macro pores but require an expensive operation. Heat treatment of surfaces is another physical method used to anneal, harden or smooth metals. Traditional metal chemical modification of a surface uses wet methods in processes such as acid etching, "pickling," and electrochemical passivation. Chemically treated surfaces typically are not desirable for use a cellular growth surfaces because of the presence of unwanted byproducts of the chemical process such as hydride layers remaining on the surface. Polymer chemical surface modifications generally involve cleaning procedures with aqueous and/or organic solvents; some machining techniques also have been used to modify polymeric surfaces, as well as heat treatment.
Electrochemical surface modification includes electroplating of materials such as nickel, copper, chrome, titanium, precious metals and/or other commonly used plating metal and metallic compounds. Other surface treatments include conventional coating techniques (i.e., spray painting, dipping, etc.) as well as vapor deposition and plasma grafting technologies. Comprehensive descriptions of the art of traditional surface treatment and finishing can be found in A Guide to Metal and Plastic Finishing (Maroney, Marion L.; 1991), Handbook of Semiconductor Electrodeposition (Applied Physics, 5) (Pandey, R. K., et. al.; 1996), Surface Finishing Systems: Metal and Non-Metal Finishing Handbook-Guide (Rudzki, George J.; 1984), and Materials and Processes for Surface and Interface Engineering (NATO Asi Series. Series E, Applied Sciences, 115) (Pauleau, Ives (Editor); 1995); herein incorporated by reference.
Cold plasmas have been used to process materials for a variety of technologies, such as metallurgy, microelectronics, and biotechnology. Plasma applications include the treatment of solid surfaces, deposition of films, surface modifications and/or dry etching of surface layers.
Plasmas are created when a sufficient amount of energy, higher than the ionization energy, is added to gaseous atoms and/or molecules, causing ionization and subsequently generating free electrons, photons, free radicals and ionic species. Often referred to as a fourth state of matter, plasmas do not exhibit the same type of phase changes as other states of matter [e.g., solid to liquid (melting), gas to liquid (condensation), or solid to gas (sublimation)]. Transition of a gas (or vapor) from an unexcited, electrically stable state to an ionized plasma state tends to occur through a continuous process rather than a distinct phase change. The excitation energy supplied to a gas to form a cold plasma can originate from electrical discharges, direct currents, radio frequencies, microwaves or other forms of electromagnetic radiation. Plasmas are characterized by the following parameters: density of neutral particles, densities of electrons and ions, energy distributions, and the degree of ionization used to pseudo-quantify charge species density.
Plasma techniques for modifying the surface characteristics of many materials are known. Specific applications for surface modified materials have been described for both microcircuit and medical implant device technology. Plasma dry etching processes are routinely used in the semiconductor and microelectronics industries. Those industries generally use plasma dry etching techniques in which unmasked regions are subjected to a clean etch utilizing relatively high power-to-surface-area ratios, ultra-low pressures and pristine conditions that result in an absence of extrinsic molecules. These conditions are used to produce a smooth, minimally defective planar surfaces. Additionally, microcircuit etching requires precise and defined etch patterns and therefore employs static masking techniques in the plasma dry etching process.
Oehrlein et al in Surface Interface Anal. 8:243 (1986) investigate the mechanism of surface roughening observed in the microelectronics industry on silicon surfaces. Oehrlein reports surface features on the order of 80 nm to 330 nm. Although Oehrlein suggests non-uniform etch rates due to involatile surface residues as the source of the surface roughness, the scale of the roughness was much less than those deem desirable in medical implant applications. This is because for the chosen target and gas used, the etch time used was insufficient to generate an etch depth deeper than 300 nm. Furthermore, Oehrlein teaches etches deeper than 300 nm are undesirable.
In the medical implant industry, the use of plasma treatment of materials has generally been confined to surface conditioning without significant attention of the surface morphology. Descriptions and elaboration of surface modifications for implants and other devices by RF plasmas can be found in the following sources and herein are incorporated by reference: U.S. Pat. Nos. 3,814,983; 4,929,319, 4,948,628; 5,055,316; 5,080,924; 5,084,151; 5,217,743; 5,229,172; 5,246,451; 5,260,093; 5,262,097; 5,364,662; 5,451,428; 5,476,509; and 5,543,019.
Many plasma treatment techniques, for polymers in particular, use cold plasmas to activate the surface by plasma-induced polymerization and/or RF plasma treatment to break surface polymer bonds. This action generates ions and free radicals, setting up favorable conditions for subsequent RF plasma-induced polymerization and grafting of monomers to the substrate surface as described in U.S. Pat. No. 5,080,924; incorporated herein by reference. In another application, similar covalent bonding of polymeric biocompatible materials onto intraocular lenses via RF plasma grafting was successfully achieved, creating a microscopically smooth surface as described in U.S. Pat. No. 5,260,093; herein incorporated in reference.
There is then, a need to modify implant substrate material surfaces so that these medical devices have the appropriate roughness, porosity and texture necessary to affix inorganic, polymeric and/or biological coatings and allow cellular in-growth into the device surface.